The most common cause of secondary adrenocorticol insufficiency is iatrogenic, caused by withdrawal of therapy from patients who have been treated with pharmocologic doses of glucocorticoids (10). Clinical experience suggests that more than 30 d of supraphysiologic glucocorticoid treatment (e.g., prednisone at doses of >7.5 mg/d) may suppress CRH and ACTH for 3-6 mo; an additional 36 mo may then be required for cortisol to respond to ACTH since ACTH is trophic for the adrenal glands. Both topical and inhaled steroids (11) have now been reported to suppress the hypothalamic-pituitary adrenal axis, so withdrawal from prolonged use of these agents must be monitored for adrenal insufficiency.
The next most common causes of secondary adrenocortical insufficiency are tumors of the pituitary and/or hypothalmic region (most commonm after surgical and radiation treatment to the pituitary) as well as lymphocytic hypophysitis, sarcoidosis, and histocytosis. In these cases, ACTH is rarely the only pituitary hormone deficiency. Patients may present with either symptoms suggestive of a cranial mass, such as headache or visual field defects, or defects in other pituitary hormones such as gonadotropins, which usually are lost first (female: irregular or absent menses; male: erectile dysfunction), followed by hypothyroid symptoms, followed finally by loss of ACTH.
Causes of acute onset of secondary adrenal insufficiency are postpartum pituitary necrosis (Sheehan's syndrome) usually associated with heavy blood loss and the need for transfusions at delivery, head trauma with shearing of the pituitary stalk, or bleeding into pituitary macroadenomas.
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